Ivermectin as a Direct Anti-Tumour Agent: Evidence, Mechanisms, and Application to Helminth-Associated Malignancies

Background: Ivermectin is a macrocyclic lactone approved for human use in parasitic infections affecting over 200 million people annually. Study 9 ([10.5281/zenodo.20402641](https://doi.org/10.5281/zenodo.20402641)) of this series documented a population-level decline in adult T-cell leukaemia/lymphoma (ATL) following mass ivermectin campaigns in Okinawa, Japan, which was attributed to clearance of Strongyloides stercoralis and consequent restoration of anti-HTLV-1 immune surveillance. However, accumulating preclinical evidence indicates that ivermectin also possesses direct anti-tumour activity through multiple, mechanistically distinct pathways operating at clinically relevant concentrations. This study asks: does ivermectin's anti-tumour pharmacology contribute independently to the Okinawa effect, and if so, does the existing model underestimate the total attributable impact of the mass programme? Methods: Systematic narrative synthesis of verified primary literature on ivermectin anti-tumour mechanisms, with specific attention to ATL and HTLV-1-infected T-cell line data; review of registered clinical trial evidence; triangulation with the Okinawa epidemiological findings...